Nov. 02--Researchers at Sarver Heart Center in Tucson reported Monday that they have discovered a possible mechanism for preventing the degradation of heart muscle that continues even after doctors restore blood flow to the heart.
The breakthrough could ultimately lead to decreased heart-muscle damage and speedier recoveries after a clot-caused heart attack.
"Time is muscle" when arteries are blocked. The more quickly you restore blood flow, the less damage done, said Dr. Gordon Ewy, director of Sarver Heart Center at the University of Arizona.
That's why doctors rush to remove artery blockages with inflatable balloons or clot-busting drugs.
But they have always known that additional damage occurs during restoration of the blood flow.
The phenomenon is called ischemia/reperfusion injury, with "ischemia" referring to the blockage and "reperfusion" to restoration of the blood flow.
Researcher Henk Granzier identified the villain in that phenomenon: a protease called MMP-2, which had previously been known to interfere with the "glue" that holds muscle cells together.
Granzier and his team found, in studies on rats, that MMP-2 was actually working within the individual cells of the heart muscle to degrade an important protein called titin.
Titin is a "molecular spring" that aids the contractions and expansions that move blood through the heart. It is the largest protein known, Granzier said.
Stretched out, it measures 10 microns and is almost visible to the human eye. Spelled out with all its components, it would form the largest word in the English language, with 33,000 characters.
Granzier has specialized in studying titin since its discovery about 20 years ago. He joined Sarver three years ago as the Alan and Alfie Norville Endowed Chair in Sarver's molecular cardiovascular research program.
After discovering that MMP-2 was degrading titin in the heart muscle of rats, Granzier's team tested "chemical inhibitors" in mouse and rat hearts. That worked to lessen the damage, he said.
The study, which concludes that drugs or genetic approaches could halt the damage, was published Monday in the journal Circulation. It was done in collaboration with a team led by Richard Schulz of the Cardiovascular Research Centre at the University of Alberta, Canada.
Funding came from the U.S. National Institutes of Health and the Alberta Heritage Research Foundation.
It's a long way from lab bench to use in the operating room, Ewy said, but he'd like to speed up the process on this one because of its remarkable potential.
The next step is testing the process with pigs, which have hearts that are are a better match to those of humans, he said.
It will take years, Ewy said, but "we're excited by this, and we're absolutely delighted that he (Granzier) is here doing this work."
"This has the potential of decreasing the amount of heart damage you get from a heart attack and decreasing heart failure down the road."
Contact reporter Tom Beal at tbeal@azstarnet.com or 573-4158.
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